A thorough knowledge of the structure and function of regenerating nerve terminals is basic to our understanding of the molecular events that underlie the regenerative process. Studies of regenerating synapses may also give insight into the mechanisms involved in the formation of nerve terminals that occurs during normal development. During the first twenty two months of this grant period, I have used anatomical and physiological techniques to study the precision of reinnervation of original synaptic sites in the cutaneous pectoris muscle of the frog after a nerve crush. This muscle is well suited for studies of this type because a) it is readily accessible for surgery and b) it is thin and transparent which enables one to see and record electrophysiologically from individual neuromuscular junctions and then to study the same neuromuscular junctions by a variety of histological and histochemical techniques including electron microscopy. Thus far the project has demonstrated that after a nerve crush nearly all of the postsynaptic membrane is covered by regenerating nerve terminals and few, if any, synapses are made elsewhere on the fiber surface. The developing terminal branches differentiate at varying rates along their length but the initial sites of differentiation are above original junctional folds. This remarkable topographic specificity is not dependent on the integrity of the muscle cell; instead the axons use cues external to the muscle cell surface, either in or attached to the muscle cell's basal lamina. My objectives during the next year are to examine further the role of the muscle in topographically precise reinnervation and the differentiation of the nerve terminal.